title: The biological characteristics and pharmacodynamics of a mycophenolate mofetil nanosuspension ophthalmic delivery system in rabbits.
abstract: The purpose of this study was to investigate corneal mucoadhesion, pharmacokinetics in lacrimal fluid and aqueous humor, the immune suppression induced by corneal transplantation of mycophenolate mofetil (MMF) nanosuspensions (NS), and the use of a chitosan-modified MMF nanosuspension (C-NS) as an ophthalmic delivery system. The results indicated that NS had a higher drug concentration in corneal muscoadhesive samples, lacrimal fluid and aqueous humor samples than the MMF ophthalmic suspension. In addition, C-NS had a much higher concentration than the NS. The mean survival time of cornea in corneal allografts was extended remarkably in the NS and C-NS trial groups. The results confirm that the C-NS and NS markedly increase corneal mucoadhesion and drug absorption, prolong the survival time of high-risk allografts, and significantly inhibit corneal immune rejection in a rabbit model of penetrating keratoplasty. In this model, C-NS was more effective than NS.
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao 266071, China. wuxianggen@126.com.
authors.forename: Xiang-Gen
authors.initials: XG
authors.lastname: Wu
authors.forename: Meng
authors.initials: M
authors.lastname: Xin
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Yang
authors.forename: Wei-Yun
authors.initials: WY
authors.lastname: Shi
mesh_terms: D000268:Adhesiveness; D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D016039:Corneal Transplantation / Q000379:methods; D016503:Drug Delivery Systems; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D049329:Nanostructures / Q000737:chemistry; D009883:Ophthalmic Solutions / Q000737:chemistry*; D011817:Rabbits
chemical_list: D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D048271:Chitosan; D009173:Mycophenolic Acid
keywords: absorption; chitosan; mucoadhesion; mucosal drug delivery; mycophenolate mofetil; mycophenolic acid; nanosuspension; pharmacodynamics; pharmacokinetics